JP2007504238A - ポリ(adp−リボース)ポリメラーゼ(parp)の阻害剤としての置換インドール - Google Patents
ポリ(adp−リボース)ポリメラーゼ(parp)の阻害剤としての置換インドール Download PDFInfo
- Publication number
- JP2007504238A JP2007504238A JP2006525431A JP2006525431A JP2007504238A JP 2007504238 A JP2007504238 A JP 2007504238A JP 2006525431 A JP2006525431 A JP 2006525431A JP 2006525431 A JP2006525431 A JP 2006525431A JP 2007504238 A JP2007504238 A JP 2007504238A
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- JP
- Japan
- Prior art keywords
- indole
- carboxaldehyde
- piperazin
- phenyl
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 239000003112 inhibitor Substances 0.000 title abstract description 10
- 150000002475 indoles Chemical class 0.000 title abstract description 8
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 title description 14
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 title description 12
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 166
- 238000000034 method Methods 0.000 claims abstract description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 201000010099 disease Diseases 0.000 claims abstract description 24
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 11
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 claims abstract description 10
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 claims abstract description 8
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 claims abstract description 8
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 claims abstract description 8
- -1 hydroxy, hydroxy Chemical group 0.000 claims description 166
- 125000000217 alkyl group Chemical group 0.000 claims description 153
- 201000006417 multiple sclerosis Diseases 0.000 claims description 108
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 41
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 21
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 208000028867 ischemia Diseases 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 19
- 125000003386 piperidinyl group Chemical group 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 18
- 125000004193 piperazinyl group Chemical group 0.000 claims description 18
- 150000002431 hydrogen Chemical group 0.000 claims description 17
- 230000004770 neurodegeneration Effects 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000002883 imidazolyl group Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 230000000451 tissue damage Effects 0.000 claims description 16
- 231100000827 tissue damage Toxicity 0.000 claims description 16
- 125000003725 azepanyl group Chemical group 0.000 claims description 15
- 125000004069 aziridinyl group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000005959 diazepanyl group Chemical group 0.000 claims description 15
- 125000002757 morpholinyl group Chemical group 0.000 claims description 15
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 15
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 14
- 125000003282 alkyl amino group Chemical group 0.000 claims description 14
- 208000006011 Stroke Diseases 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 125000004001 thioalkyl group Chemical group 0.000 claims description 13
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 12
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 12
- LDEZMLOFINBHDP-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 LDEZMLOFINBHDP-UHFFFAOYSA-N 0.000 claims description 11
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 11
- 208000012902 Nervous system disease Diseases 0.000 claims description 11
- 230000032683 aging Effects 0.000 claims description 11
- 125000001624 naphthyl group Chemical group 0.000 claims description 11
- 230000001537 neural effect Effects 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 11
- 208000025966 Neurological disease Diseases 0.000 claims description 10
- 230000006378 damage Effects 0.000 claims description 10
- 206010012601 diabetes mellitus Diseases 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- KISOWYLWDNQSTC-UHFFFAOYSA-N 1-phenyl-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C=1C=CC=CC=1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 KISOWYLWDNQSTC-UHFFFAOYSA-N 0.000 claims description 8
- 201000006474 Brain Ischemia Diseases 0.000 claims description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 8
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 8
- 206010008118 cerebral infarction Diseases 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 231100000419 toxicity Toxicity 0.000 claims description 8
- 230000001988 toxicity Effects 0.000 claims description 8
- RTVKFYOHDDENLY-UHFFFAOYSA-N 1-(3-bromophenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound BrC1=CC=CC(N2C3=CC=CC=C3C(C=O)=C2N2CCNCC2)=C1 RTVKFYOHDDENLY-UHFFFAOYSA-N 0.000 claims description 7
- KDUUBUWHTWGOLL-UHFFFAOYSA-N 1-(3-ethoxyphenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound CCOC1=CC=CC(N2C3=CC=CC=C3C(C=O)=C2N2CCNCC2)=C1 KDUUBUWHTWGOLL-UHFFFAOYSA-N 0.000 claims description 7
- MHRXAACLXPGLKM-UHFFFAOYSA-N 1-(3-formylphenyl)-2-piperazin-2-ylindole-3-carbaldehyde Chemical compound C=1C=CC(C=O)=CC=1N1C2=CC=CC=C2C(C=O)=C1C1CNCCN1 MHRXAACLXPGLKM-UHFFFAOYSA-N 0.000 claims description 7
- NAEKHISYDJUGPG-UHFFFAOYSA-N 1-(4-ethenylphenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C1=CC(C=C)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 NAEKHISYDJUGPG-UHFFFAOYSA-N 0.000 claims description 7
- ABRVLRXWOMATLP-UHFFFAOYSA-N 1-(4-methylphenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C1=CC(C)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 ABRVLRXWOMATLP-UHFFFAOYSA-N 0.000 claims description 7
- VYYDEFMPUVDYKB-UHFFFAOYSA-N 1-[3-(hydroxymethyl)phenyl]-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound OCC1=CC=CC(N2C3=CC=CC=C3C(C=O)=C2N2CCNCC2)=C1 VYYDEFMPUVDYKB-UHFFFAOYSA-N 0.000 claims description 7
- KDNOFJMPZXANKH-UHFFFAOYSA-N 1-[4-(dimethylamino)phenyl]-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C1=CC(N(C)C)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 KDNOFJMPZXANKH-UHFFFAOYSA-N 0.000 claims description 7
- 206010019196 Head injury Diseases 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 206010063837 Reperfusion injury Diseases 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 7
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 7
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 7
- 230000030833 cell death Effects 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 210000002569 neuron Anatomy 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- VDLQBSZIIISXBW-UHFFFAOYSA-N 1-(3-chlorophenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound ClC1=CC=CC(N2C3=CC=CC=C3C(C=O)=C2N2CCNCC2)=C1 VDLQBSZIIISXBW-UHFFFAOYSA-N 0.000 claims description 6
- ADEITXPPRLSGJO-UHFFFAOYSA-N 1-(4-ethylphenyl)-2-piperazin-1-ylindole-3-carbaldehyde;hydrochloride Chemical compound Cl.C1=CC(CC)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 ADEITXPPRLSGJO-UHFFFAOYSA-N 0.000 claims description 6
- RXBAMRONNKVCOX-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-piperazin-1-ylindole-3-carbaldehyde;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 RXBAMRONNKVCOX-UHFFFAOYSA-N 0.000 claims description 6
- XFFNUTFXHKDOHN-UHFFFAOYSA-N 1-(4-phenoxyphenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 XFFNUTFXHKDOHN-UHFFFAOYSA-N 0.000 claims description 6
- DUDUOCYPAJBUEM-UHFFFAOYSA-N 1-(4-phenylphenyl)-2-piperazin-1-ylindole-3-carbaldehyde;hydrochloride Chemical compound Cl.C=1C=C(C=2C=CC=CC=2)C=CC=1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 DUDUOCYPAJBUEM-UHFFFAOYSA-N 0.000 claims description 6
- RIRLLQPWWGOVPZ-UHFFFAOYSA-N 1-(benzenesulfonyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C=1C=CC=CC=1S(=O)(=O)N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 RIRLLQPWWGOVPZ-UHFFFAOYSA-N 0.000 claims description 6
- JKRHWIFUFYPMGU-UHFFFAOYSA-N 1-phenyl-2-piperazin-1-yl-2,3-dihydropyrrolo[2,3-b]pyridine-3-carbaldehyde Chemical compound C12=NC=CC=C2C(C=O)C(N2CCNCC2)N1C1=CC=CC=C1 JKRHWIFUFYPMGU-UHFFFAOYSA-N 0.000 claims description 6
- LHJGUJXHCDLPTA-UHFFFAOYSA-N 1-phenyl-2-piperazin-1-ylpyrrolo[2,3-c]pyridine-3-carbaldehyde Chemical compound C=1C=CC=CC=1N1C2=CN=CC=C2C(C=O)=C1N1CCNCC1 LHJGUJXHCDLPTA-UHFFFAOYSA-N 0.000 claims description 6
- HVSOWMPVDIZSNW-UHFFFAOYSA-N 2-piperazin-1-yl-1-pyridin-2-ylindole-3-carbaldehyde Chemical compound C=1C=CC=NC=1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 HVSOWMPVDIZSNW-UHFFFAOYSA-N 0.000 claims description 6
- JIZOTZUBOYLPIC-UHFFFAOYSA-N 2-piperazin-1-yl-1-thiophen-3-ylindole-3-carbaldehyde Chemical compound C1=CSC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 JIZOTZUBOYLPIC-UHFFFAOYSA-N 0.000 claims description 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- 210000000944 nerve tissue Anatomy 0.000 claims description 6
- 125000000466 oxiranyl group Chemical group 0.000 claims description 6
- 208000032253 retinal ischemia Diseases 0.000 claims description 6
- BTYLHGKONBTRGB-UHFFFAOYSA-N tert-butyl 4-[3-formyl-1-(4-iodophenyl)indol-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=O)C2=CC=CC=C2N1C1=CC=C(I)C=C1 BTYLHGKONBTRGB-UHFFFAOYSA-N 0.000 claims description 6
- NGSVSMRDRNVJHY-UHFFFAOYSA-N tert-butyl 4-[3-formyl-1-[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrol-2-yl]phenyl]indol-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=O)C2=CC=CC=C2N1C1=CC=C(C=2N(C=CC=2)C(=O)OC(C)(C)C)C=C1 NGSVSMRDRNVJHY-UHFFFAOYSA-N 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- DXOVMFAJBGGUTH-UHFFFAOYSA-N 1-(4-butylphenyl)-2-piperazin-1-ylindole-3-carbaldehyde;hydrochloride Chemical compound Cl.C1=CC(CCCC)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 DXOVMFAJBGGUTH-UHFFFAOYSA-N 0.000 claims description 5
- XVOOCCYPMVCNJO-UHFFFAOYSA-N 1-(4-methyl-3-nitrophenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C1=C([N+]([O-])=O)C(C)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 XVOOCCYPMVCNJO-UHFFFAOYSA-N 0.000 claims description 5
- YBUNFPZHXACSJP-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-2-(2-methylaziridin-1-yl)indole-3-carbaldehyde Chemical compound CC1CN1C1=C(C=O)C2=CC=CC=C2N1C1=CC=C(C(C)(C)C)C=C1 YBUNFPZHXACSJP-UHFFFAOYSA-N 0.000 claims description 5
- ZDTLOYLZXLCULU-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-2-(4-methylpiperazin-1-yl)indole-3-carbaldehyde Chemical compound C1CN(C)CCN1C1=C(C=O)C2=CC=CC=C2N1C1=CC=C(C(C)(C)C)C=C1 ZDTLOYLZXLCULU-UHFFFAOYSA-N 0.000 claims description 5
- YELWFIMFXVYHHI-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-2-[2-(dimethylamino)ethylamino]indole-3-carbaldehyde Chemical compound CN(C)CCNC1=C(C=O)C2=CC=CC=C2N1C1=CC=C(C(C)(C)C)C=C1 YELWFIMFXVYHHI-UHFFFAOYSA-N 0.000 claims description 5
- IZMRDIIAFAXFFD-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-2-[4-(2-hydroxyethyl)piperazin-1-yl]indole-3-carbaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCN(CCO)CC1 IZMRDIIAFAXFFD-UHFFFAOYSA-N 0.000 claims description 5
- QSHPKLKHZNKMCA-UHFFFAOYSA-N 2-(1,4-diazepan-1-yl)-1-phenylpyrrolo[2,3-b]pyridine-3-carbaldehyde;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C=1C=CC=CC=1N1C2=NC=CC=C2C(C=O)=C1N1CCCNCC1 QSHPKLKHZNKMCA-UHFFFAOYSA-N 0.000 claims description 5
- GBSBKSABVLLECH-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]-1-phenylindole-3-carbaldehyde Chemical compound C1CN(CCO)CCN1C1=C(C=O)C2=CC=CC=C2N1C1=CC=CC=C1 GBSBKSABVLLECH-UHFFFAOYSA-N 0.000 claims description 5
- XHLZFJZRYMLALS-UHFFFAOYSA-N 2-piperazin-1-yl-1-(4-pyridin-4-ylphenyl)indole-3-carbaldehyde Chemical compound C=1C=C(C=2C=CN=CC=2)C=CC=1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 XHLZFJZRYMLALS-UHFFFAOYSA-N 0.000 claims description 5
- RHQCRGLZLYXZRF-UHFFFAOYSA-N 2-piperazin-1-yl-1-pyridin-3-ylindole-3-carbaldehyde Chemical compound C=1C=CN=CC=1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 RHQCRGLZLYXZRF-UHFFFAOYSA-N 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 5
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 claims description 5
- 206010028851 Necrosis Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 5
- 208000027418 Wounds and injury Diseases 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 5
- 208000031225 myocardial ischemia Diseases 0.000 claims description 5
- UGFOUQSTKUFUJM-UHFFFAOYSA-N n-[3-(3-formyl-2-piperazin-1-ylindol-1-yl)phenyl]acetamide;hydrochloride Chemical compound Cl.CC(=O)NC1=CC=CC(N2C3=CC=CC=C3C(C=O)=C2N2CCNCC2)=C1 UGFOUQSTKUFUJM-UHFFFAOYSA-N 0.000 claims description 5
- 230000017074 necrotic cell death Effects 0.000 claims description 5
- 210000005036 nerve Anatomy 0.000 claims description 5
- UGNQPDYJCPTLDE-UHFFFAOYSA-N tert-butyl 4-[1-(4-tert-butylphenyl)-3-formylindol-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=C(C=O)C2=CC=CC=C2N1C1=CC=C(C(C)(C)C)C=C1 UGNQPDYJCPTLDE-UHFFFAOYSA-N 0.000 claims description 5
- 230000009529 traumatic brain injury Effects 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 5
- TUJQMOFASNTKCI-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C1=C(Cl)C(F)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 TUJQMOFASNTKCI-UHFFFAOYSA-N 0.000 claims description 4
- PQDSQQXPUZSZKE-UHFFFAOYSA-N 1-(3-fluorophenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound FC1=CC=CC(N2C3=CC=CC=C3C(C=O)=C2N2CCNCC2)=C1 PQDSQQXPUZSZKE-UHFFFAOYSA-N 0.000 claims description 4
- DKAWAJFCEOEMAR-UHFFFAOYSA-N 1-(3-methoxyphenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound COC1=CC=CC(N2C3=CC=CC=C3C(C=O)=C2N2CCNCC2)=C1 DKAWAJFCEOEMAR-UHFFFAOYSA-N 0.000 claims description 4
- FSJDZNKZFVFUKS-UHFFFAOYSA-N 1-(3-methylphenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound CC1=CC=CC(N2C3=CC=CC=C3C(C=O)=C2N2CCNCC2)=C1 FSJDZNKZFVFUKS-UHFFFAOYSA-N 0.000 claims description 4
- VXENHVARWXTNRL-UHFFFAOYSA-N 1-(3-nitrophenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(N2C3=CC=CC=C3C(C=O)=C2N2CCNCC2)=C1 VXENHVARWXTNRL-UHFFFAOYSA-N 0.000 claims description 4
- XRQJZQZNANNIPN-UHFFFAOYSA-N 1-(4-bromophenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C1=CC(Br)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 XRQJZQZNANNIPN-UHFFFAOYSA-N 0.000 claims description 4
- CEAABTIHBZDCGZ-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C1=CC(Cl)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 CEAABTIHBZDCGZ-UHFFFAOYSA-N 0.000 claims description 4
- RJLPQPYGSOUPPM-UHFFFAOYSA-N 1-(4-methoxyphenyl)-2-piperazin-1-ylindole-3-carbaldehyde Chemical compound C1=CC(OC)=CC=C1N1C2=CC=CC=C2C(C=O)=C1N1CCNCC1 RJLPQPYGSOUPPM-UHFFFAOYSA-N 0.000 claims description 4
- VBIZIJRQONZXME-UHFFFAOYSA-N 1-(4-tert-butylphenyl)-2-(2-pyrrolidin-1-ylethylamino)indole-3-carbaldehyde;hydrochloride Chemical compound Cl.C1=CC(C(C)(C)C)=CC=C1N1C2=CC=CC=C2C(C=O)=C1NCCN1CCCC1 VBIZIJRQONZXME-UHFFFAOYSA-N 0.000 claims description 4
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- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2010007972A1 (ja) * | 2008-07-14 | 2010-01-21 | 参天製薬株式会社 | カルバモイル基、ウレイド基及び置換オキシ基を有する新規インドール誘導体 |
JP2011512340A (ja) * | 2008-02-15 | 2011-04-21 | エフ.ホフマン−ラ ロシュ アーゲー | 3−アルキルピペラジン誘導体及びその使用 |
JP2011148751A (ja) * | 2010-01-25 | 2011-08-04 | Konica Minolta Holdings Inc | 含窒素縮合複素環化合物の製造方法 |
JP2016510800A (ja) * | 2013-03-13 | 2016-04-11 | プロクシマゲン リミテッド | 新規化合物 |
Families Citing this family (64)
Publication number | Priority date | Publication date | Assignee | Title |
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Also Published As
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US20080255350A1 (en) | 2008-10-16 |
US8008491B2 (en) | 2011-08-30 |
CN1870991A (zh) | 2006-11-29 |
WO2005023246A1 (en) | 2005-03-17 |
AU2004270187A1 (en) | 2005-03-17 |
IL173917A0 (en) | 2006-07-05 |
KR20060088102A (ko) | 2006-08-03 |
US7405300B2 (en) | 2008-07-29 |
BRPI0414136A (pt) | 2006-10-31 |
MXPA06002499A (es) | 2006-06-20 |
CA2537097A1 (en) | 2005-03-17 |
EP1663202A1 (en) | 2006-06-07 |
US20050054631A1 (en) | 2005-03-10 |
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